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GSE11622
Homo sapiens, Rattus norvegicus
98 Downloadable Samples
Affymetrix Rat Expression 230A Array (rae230a)
Description
Background. Vaginal atrophy (VA) is the thinning of the vaginal epithelial lining, typically the result of lowered estrogen levels during menopause. Some of the consequences of VA include increased susceptibility to bacterial infection, pain during sexual intercourse, and vaginal burning or itching. Although estrogen treatment is highly effective, alternative therapies are also desired for women who are not candidates for hormone replacement therapy (HRT). The ovariectomized (OVX) rat is widely accepted as an appropriate animal model for many estrogen-dependent responses in humans; however, since reproductive biology can vary significantly between mammalian systems, this study examined how well the OVX rat recapitulates human biology at the transcriptional level. This report describes an analysis of expression profiling data, comparing the responses of rat and human vaginae to estrogen treatment. Results. The level of differential expression between pre- vs. post- estrogen treatment was calculated for each of the human and OVX rat datasets. Probe sets corresponding to orthologous rat and human genes were mapped to each other using NCBI Homologene. A positive correlation was observed between the rat and human responses to estrogen. Genes belonging to several biological pathways and GO categories were similarly differentially expressed in rat and human. A large number of the coordinately regulated biological processes are already known to be involved in human VA, such as inflammation, epithelial development, and EGF pathway activation. Conclusions. At the transcriptional level, there is evidence of significant overlap of the effects of estrogen treatment between the OVX rat and human VA samples.
Publication Title
Molecular analysis of the vaginal response to estrogens in the ovariectomized rat and postmenopausal woman.
Sample Metadata Fields
Age
View Samples- Homo sapiens, Rattus norvegicus
- 106 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Uterine leiomyomata, or fibroids, are benign tumors of the uterine myometrium that significantly affect up to 30% of reproductive-age women. Despite being the primary cause of hysterectomy in the United States, accounting for up to 200,000 procedures annually, the etiology of leiomyoma remains largely unknown. Due to the lack of an effective medicinal therapy for these tumors, this disease continues to have a tremendous negative impact on womens health. As a basis for understanding leiomyoma pathogenesis and identifying targets for pharmacotherapy, we conducted transcriptional profiling of leiomyoma and unaffected myometrium from humans and Eker rats, the best characterized preclinical model of leiomyoma. A global comparison of mRNA from leiomyoma versus myometrium in human and rat identified a highly significant overlap of dysregulated gene expression in leiomyoma. An unbiased pathway analysis using a method of gene set enrichment based on the Sigpathway algorithm detected the mammalian target of rapamycin (mTOR) pathway as one of the most highly upregulated pathways in both human and rat tumors. Activation of this pathway was confirmed in both human and rat leiomyomata at the protein level via Western. Inhibition of mTOR in female Eker rats with the rapamycin analog WAY-129327 for 2 weeks decreased mTOR signaling and cell proliferation in tumors, and treatment for 4 months significantly decreased tumor incidence, multiplicity and size. These results identify dysregulated mTOR signaling as a component of leiomyoma etiology across species and directly demonstrate the dependence of these tumors on mTOR signaling for growth in the Eker rat. Modulation of this pathway warrants additional investigation as a potential therapy for uterine leiomyoma.
Publication Title
Comparison of human and rat uterine leiomyomata: identification of a dysregulated mammalian target of rapamycin pathway.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Peripheral whole blood-based gene expression profiling has become one of the most common strategies exploited in the development of clinically relevant biomarkers. However, the ability to identify biologically meaningful conclusions from gene expression patterns in whole blood is highly problematic. First, it is difficult to know whether or not expression patterns in whole blood capture those in primary tissues. Second, if explicit steps are not taken to accommodate the extremely elevated expression levels of globin in blood then large-scale multi-probe microarray-based studies can be severely compromised. Many studies consider the use of mouse blood as a model for human blood in addition to considering blood gene expression levels as a general surrogate for gene expression levels in other tissues. We explored the effects of globin reduction on peripheral mouse blood in the detection of genes known to be expressed in human tissues. Globin reduction resulted in 1.) a significant increase in the number of probes detected (5840 944 vs 12411 1904); 2.) increased expression for 4128 probe sets compared to non-globin reduced blood (p < .001, two-fold); 3.) improved detection of genes associated with many biological pathways and diseases; and 4.) an increased ability to detect genes expressed in 27 human tissues (p < 10-4). This study suggests that although microarray-based mouse blood gene expression studies that do not consider the effects of globin are severely compromised, globin-reduced mouse whole blood gene expression studies can be used to capture the expression profiles of genes known to contribute to various human diseases.
Publication Title
The effects of globin on microarray-based gene expression analysis of mouse blood.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 143 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
Comparison between in vitro transcription- and cDNA-mediated annealing, selection and ligation (DASL)-based assays on brain-specific reference RNA, and postmortem frozen and formalin fixed brain tissue from autistic and control cases. Investigation of data preprocessing techniques for DASL-assayed RNA samples from frozen brain tissue.
Publication Title
Preprocessing and Quality Control Strategies for Illumina DASL Assay-Based Brain Gene Expression Studies with Semi-Degraded Samples.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 64 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
Microarray-based gene expression analysis of peripheral whole blood is a common strategy in the development of clinically relevant biomarker panels for a variety of human diseases. However, the results of such an analysis are often plagued by decreased sensitivity and reliability due to the effects of relatively high levels of globin mRNA in whole blood. Globin reduction assays have been shown to overcome such effects, but they require large amounts of total RNA and may induce distinct gene expression profiles. The Illumina whole-genome DASL (WG-DASL) assay can detect gene expression levels using partially degraded RNA samples and has the potential to detect rare transcripts present in highly heterogeneous whole blood samples without the need for globin reduction. We therefore assessed the utility of the WG-DASL assay in the analysis of peripheral whole blood gene expression profiles. We find that gene expression detection is significantly increased with the use of WG-DASL compared to the standard in vitro transcription-based direct hybridization (IVT), while globin-probe-negative WG-DASL did not exhibit significant improvements over globin-probe-positive WG-DASL. Globin reduction increases the detection sensitivity and reliability of both WG-DASL and IVT with little effect on raw intensity correlations: raw intensity correlations between total RNA and globin-reduced RNA were 0.970 for IVT and 0.981 for WG-DASL. Overall, the detection sensitivity of the WG-DASL assay is higher than the IVT-based direct hybridization assay, with or without globin reduction, and should be considered in conjunction with globin reduction methods for future blood-based gene expression studies.
Publication Title
Gene expression profiling of human whole blood samples with the Illumina WG-DASL assay.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 33 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
The 6-hydroxydopamine (6OHDA) rat model of parkinsonism is among the first, and most commonly used, animal models of Parkinsons disease. It provides insight into the compensatory changes that occur in the brain after dopamine (DA) neuron degeneration. In order to better define the consequences of substantia nigra DA neuron loss on the neural and glial populations during and following nigrostriatal degeneration, tissue was collected and evaluated from the substantia nigra of 6OHDA or vehicle treated, or nave rats at 1, 2, 4, 6 & 16 weeks.
Publication Title
The longitudinal transcriptomic response of the substantia nigra to intrastriatal 6-hydroxydopamine reveals significant upregulation of regeneration-associated genes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 72 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Microarray analysis to globally assess gene expression at the maternal-fetal interface
Publication Title
Gene expression profiling of the human maternal-fetal interface reveals dramatic changes between midgestation and term.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Preeclampsia (PE), which affects 4-8% of human pregnancies, causes significant maternal and neonatal morbidity and mortality. Within the basal plate, placental cytotrophoblasts (CTBs) of fetal origin invade the uterus and extensively remodel the maternal vasculature. In PE, CTB invasion is often shallow, and vascular remodeling is rudimentary. To better understand possible causes, we conducted a global analysis of gene expression at the maternal-fetal interface in placental samples from women with PE (n = 12; 24-36 wk) vs. samples from women who delivered due to preterm labor with no evidence of infection (n = 11; 24-36 wk), a condition that our previous work showed is associated with normal CTB invasion. Using the HG-U133A&B Affymetrix GeneChip platform, and statistical significance set at log odds-ratio of B >0, 55 genes were differentially expressed in PE. They encoded proteins previously associated with PE [e.g. Flt-1 (vascular endothelial growth factor receptor-1), leptin, CRH, and inhibin] and novel molecules [e.g. sialic acid binding Ig-like lectin 6 (Siglec-6), a potential leptin receptor, and pappalysin-2 (PAPP-A2), a protease that cleaves IGF-binding proteins]. We used quantitative PCR to validate the expression patterns of a subset of the genes. At the protein level, we confirmed PE-related changes in the expression of Siglec-6 and PAPP-A2, which localized to invasive CTBs and syncytiotrophoblasts. Notably, Siglec-6 placental expression is uniquely human, as is spontaneous PE. The functional significance of these novel observations may provide new insights into the pathogenesis of PE, and assaying the circulating levels of these proteins could have clinical utility for predicting and/or diagnosing PE.
Publication Title
Severe preeclampsia-related changes in gene expression at the maternal-fetal interface include sialic acid-binding immunoglobulin-like lectin-6 and pappalysin-2.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The aim was to identify genes that were commonly influenced by a siRNA targeting PRKCD in breast cancer cell lines.
Publication Title
Down Regulation of CLDND1 Induces Apoptosis in Breast Cancer Cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
The robust and consistent expression of the CD13 cell surface marker on very early as well as differentiated myeloid hematopoietic cells has prompted numerous investigations seeking to define roles for CD13 in myeloid cells. To directly address the function of myeloid CD13 we created a CD13 null mouse and assessed the responses of purified primary macrophages or dendritic cells from wild type and CD13 null animals in cell assays and inflammatory disease models where CD13 has been previously implicated. We find that mice lacking CD13 develop normally with normal hematopoietic profiles. Moreover, in in vitro assays, CD13 appears to be largely dispensable for the aspects of phagocytosis, proliferation and antigen presentation that we tested, but may contribute to adhesion to endothelial cells. In vivo assessment of four inflammatory disease models showed that lack of CD13 has little effect on disease onset or progression. Nominal alterations in gene expression levels between CD13 wild type and null macrophages argue against compensatory mechanisms. Analysis of the dataset with Ingenuity Pathway Analysis software did not suggest that loss of CD13 resulted in a purturbation of any specific biological pathways, processes or networks. Therefore, while CD13 is highly expressed on myeloid cells and is a reliable marker of the myeloid lineage of both normal and leukemic cells, it is not a critical regulator of hematopoietic development, hemostasis or myeloid cell function.
Publication Title
CD13 is dispensable for normal hematopoiesis and myeloid cell functions in the mouse.
Sample Metadata Fields
Specimen part
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